Sphingosine 1-phosphate is a metabolite of sphingolipid which is a physiologically active substance secreted from an activated platelet (Annual Review Biochemistry, 2004, Vol. 73, pp. 321-354). The sphingosine 1-phosphate receptor is a G-protein-binding type, and belongs to an Edg-family which is the endothelial differentiation gene. Up to now, five receptors of S1P1 (Edg1), S1P2 (Edg5), S1P3 (Edg3), S1P4 (Edg6), and S1P5 (Edg8) have been found. All of these receptors are broadly distributed in cells and tissues throughout the body, but S1P1, S1P3, and S1P4 are predominantly expressed in lymphocyte and endothelial cells, S1P2 is predominantly expressed in vascular smooth muscle cells, S1P5 is predominantly expressed in brain and spleen, and amino acid sequences thereof are well-conserved among humans and rodents (Annual Review Biochemistry, 2004, Vol. 73, pp. 321-354).
Many receptors bind to G-proteins by stimulation of sphingosine 1-phosphate. S1P1 binds to Gi/0, S1P2 and S1P3 binds to Gi/0, Gq, G12/13, and Gs, S1P4 binds to Gi/0 G12/13, and Gs, S1P5 binds to Gi/0 and G12/13, and cell proliferation caused by activation of MAPK, changes in the cytoskeletal system and cell infiltration caused by activation of Rac (and/or Rho), and production of cytokine and mediators caused by activation of PLC and calcium influx into cell, and the like (Annual Review Biochemistry, 2004, Vol. 73, pp. 321-354) are induced.
It has been known that through the stimulating action of S1P1 of sphingosine 1-phosphate, migration of lymphocyte, inhibition of apoptosis, production of cytokine, and sequestration of lymphocytes in the thymus and other secondary lymphoid tissues are induced, and angioplasty in vascular endothelial cells is promoted (Nature Review Immunology, 2005, Vol. 5, pp. 560-570). On the other hand, expression of S1P3 is also found on cardiomyocyte, and a transient decrease in the heart rate (infrequent pulse) or in the blood pressure through the stimulation of sphingosine 1-phosphate is observed (Japanese Journal of Pharmacology, 2000, Vol. 82, pp. 338-342). Infrequent pulse is not observed through the stimulation of sphingosine 1-phosphate in knockout mice wherein S1P3 is genetically deficient (Journal of Pharmacology and Experimental Therapeutics, 2004, Vol. 309, pp. 758-768).
It has been known that FTY720 and an FTY720 phosphate which is an active main body thereof have an excellent S1P1 agonist action and thus induce lymphocyte sequestration, and their effects on skin graft or multiple sclerosis, which are autoimmune diseases, is reported (Cellular & Molecular Immunology, 2005, Vol. 2, No. 6, pp. 439-448; and The New England Journal of Medicine, 2006, Vol. 355, pp. 1124-40). However, there have also been reported side effects such as infrequent pulse, reduced lung function (Transplantation, 2006, 82, pp. 1689-1967). It is reported that the FTY720 phosphate has a non-selective agonist action on S1P3, S1P4, and S1P5 (Science, 2002, Vol. 296, pp. 346-349), and between them, a clinical trial result that infrequent pulse induced by a stimulating action through S1P3 is expressed with high frequency as an undesirable side-effect has been reported (Journal of American Society of Nephrology, 2002, Vol. 13, pp. 1073-1083).
As a compound having an S1P1 agonist action, Patent Document 1 discloses a compound of the following general formula (A):

[wherein n represents 1 or 2; A represents —C(O)OR9 or the like; R9 represents hydrogen or alkyl; X represents a bond, C1-4 alkylene, —X1OX2—, or the like, in which X1 and X2 are independently selected from a bond and C1-3 alkylene; Y represents a condensed 5,6- or 6,6-hetero bicyclic ring system containing at least one aromatic ring, in which the condensed bicyclic ring system of Y may be substituted, if desired; R1 is selected from C6-10 aryl and C2-9 heteroaryl, in which any aryl or heteroaryl is substituted with C6-10 aryl C0-4 alkyl, C2-9 heteroaryl, C0-4 alkyl, C1-6 alkyl, or the like, if desired, R2, R3, R5, R6, R7, and R8 independently represent hydrogen, C1-6 alkyl, halo, or the like; R4 represents hydrogen or C1-6 alkyl; or R7 and any one of R2, R4 or R5 are combined with an atom to which they bind to form a 4- to 7-membered ring; in which the 4- to 7-membered ring is saturated or partially unsaturated] and a pharmaceutically acceptable salt, a hydrate, a solvate, an isomer, and a prodrug thereof (for details, refer to Patent Document 1), and as a specific compound thereof, for example, the benzothienyl compound above is disclosed as Example 1.
Furthermore, Patent Document 2 discloses that a compound of the following general formula (B):

[in the general formula, Ring A represents a cyclic group; Ring B represents a cyclic group which may have a substituent; X represents a spacer having one to eight atoms in the main chain, or the like; Y represents a spacer having one to ten atoms in the main chain, or the like; n represents 0 or 1; in the case where n is 0, m represents 1, and further, R1 represents a hydrogen atom or a substituent; in the case where n is 1, m represents 0 or an integer of 1 to 7, and further, R1 represents a substituent (when m is 2 or more, a plurality of R1 may be the same as or different from each other)], a salt thereof, a solvate thereof, or a prodrug thereof (for details, refer to Patent Document 2) has an S1P receptor-binding ability, and as a specific compound thereof, for example, a tetrahydronaphthalene derivative is disclosed as Example 31-06.
Moreover, Patent Document 3 discloses that a compound of the following general formula (C):

[wherein Ring A represents a cyclic group, Ring B represents a cyclic group which may further have a substituent, X represents a binding arm or a spacer having one to eight atoms in the main chain, in which one atom of the spacer may be combined with a substituent of the Ring B to form a ring which may have a substituent, Y represents a binding arm or a spacer having one to ten atoms in the main chain, in which one atom of the spacer may be combined with a substituent of the Ring B to form a ring which may have a substituent, Z represents an acidic group which may be protected, and n represents 0 or 1, provided that in the case where n is 0, m represents 1, and further, R1 represents a hydrogen atom or a substituent, in the case where n is 1, m represents 0 or an integer of 1 to 7, and further, R1 represents a substituent (when m is 2 or more, a plurality of R1s may be the same as or different from each other)], a salt thereof, an N-oxide thereof, a solvate thereof, or a prodrug thereof as a compound having an S1P receptor-binding ability. As a specific compound thereof, for example, a tetrahydronaphthalene derivative represented by Example 37-6 is disclosed.
However, up to now, there has been a desire for a novel and highly stable S1P1 agonist having the potent S1P1 agonist action of a sphingosine 1-phosphate, and correspondingly, having an excellent lymphocyte sequestering action, and further, having no undesirable actions such as infrequent pulse, reduced lung function, and the like, which have been reported with regard to conventional S1P1 agonists.